2 juni 2012: Als u hier klikt kunt u het volledige studie rapport van onderstaande studie gratis inzien. Onderaan dit artikel is een referentielijst toegevoegd.

5 september 2005: Bron; Ann Surg. 2005 Aug;242(2):178-87.

Wanneer darmkankerpatiënten geopereerd zijn en daarna als behandeling 5-FU plus levamisole plus aanvullend Folinic Acid - vorm van foliumzuur krijgen hebben ze 9,5% langere ziektevrije tijd en 11,3 % meer overleeft de darmkanker dan zonder folinic acid als aanvulling. Wanneer echter aan 5-FU plus levamisol INF = interferon-alpha wordt toegevoegd is het therapeutische effect niet noemenswaardig en de ernstige bijwerkingen worden verhoogd van 9,9% naar 30,7%. De onderzoekers pleiten dan ook voor aanvullend folinic acid naast 5-FU plus levamisol bij geopereerde darmkankerpatiënten i.p.v. het gebruikelijke interferon alpha. Hier een zo goed als letterlijke vertaling van de resultaten en conclusie uit deze grote gerandomiseerde fase III studie.

RESULTATEN:
Een totaal van 855 van de gestarte 904 patiënten (94.6%) waren beschikbaar voor evaluatie van deze studie. De mediane follow-up van alle evalueerbare patiënten was 4,6 jaar. Aanvulling van FA op 5-FU + LEV (Levamisol) verbeterde de ziektevrije en overall overleving in vergelijking met 5-FU + LEV alleen (P = 0.007 en P = 0.004, respectievelijk, 1-zijdig).

De 5-jaars overall overlevingscijfers waren 60,5% (95% confidence interval, 54.3-66.7) en 72.0% (95% confidence interval, 66.5-77.5) voor 5-FU + LEV en 5-FU + LEV + FA, respectievelijk. Aanvulling van INF-alpha (Interferong Alpha) toonde een tendens naar verbetering van ziektevrije tijd echter zonder de overall overleving te beïnvloeden. Ernstige bijwerkingen (WHO III + IV) waren in het algemeen acceptabel behalve 1 sterfgeval in de controlegroep. Ernstige bijwerkingen werden gezien bij 9,9% van de patiënten in de controlegroep die 5-FU + LEV alleen ontvingen en bij 13.3% en 30.7% bij de patiënten die respectievelijk foliumzuur (FA) en interferon alpha (INF) kregen toegediend.

CONCLUSIES:
Aanvulling met IFN-alpha wordt geassocieerd met verhoogde toxiciteit (ernstige bijwerkingen) zonder aangetoonde invloed op de effectiviteit en moet daarom niet worden geadviseerd als aanvullende behandeling. Aanvulling met foliumzuur - FA verbeterde de 5-jaars ziektevrije tijd en de overall overleving met respectievelijk 9.3% and 11.5%.

5-FU + LEV + FA gedurende 12 maanden kan een effectieve aanvullende post operatieve behandeling zijn voor lokaal gevorderde hoog risicovolle darmkanker.

Hier het originele abstract. Als u hier klikt kunt u het volledige studie rapport gratis inzien.

Addition of Folinic Acid increased the 5-year recurrence-free and overall survival rate by 9.3 and 11.5 percentage points, respectively. 5-FU + LEV + FA for 12 months may be an effective adjuvant treatment option for locally advanced high-risk colon cancer.

 Ann Surg. 2005 August; 242(2): 178–187.
PMCID: PMC1357722

Increase of Survival Benefit in Advanced Resectable Colon Cancer by Extent of Adjuvant Treatment

Results of a Randomized Trial Comparing Modulation of 5-FU + Levamisole With Folinic Acid or With Interferon-α
Karl-Heinz Link, MD,* Marko Kornmann, MD,* Ludger Staib, MD,* Martin Redenbacher, MD,† Martina Kron, PhD,‡ and Hans Günter Beger, MD*
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Abstract

Background:

The benefit of adjuvant therapy in curatively resected lymph node-positive colon cancer was established using 5-fluorouracil (5-FU) and levamisole (LEV) for 12 months. 5-FU cytotoxicity can be modulated by folinic acid (FA) or interferon-α (INF-α). The aim of this study was to investigate the efficacy of modulating 5-FU+ LEV by either FA or IFN-α in the adjuvant treatment of high-risk colon cancer.

Methods:

Patients with curatively resected colon cancer (stages UICC IIb and III) were stratified according to T, N, and participating center and randomized to receive a 12-month treatment using 5-FU + LEV alone or in combination with FA or IFN-α.

Results:

A total of 855 of 904 entered patients (94.6%) were eligible. The median follow-up of all eligible patients was 4.6 years. Addition of FA to 5-FU + LEV improved recurrence-free and overall survival in comparison with 5-FU + LEV alone (P = 0.007 and P = 0.004, respectively, 1-sided). The 5-year overall survival rates were 60.5% (95% confidence interval, 54.3–66.7) and 72.0% (95% confidence interval, 66.5–77.5) for 5-FU + LEV and 5-FU + LEV + FA, respectively. Addition of INF-α showed a tendency to improve recurrence-free survival, however, without altering overall survival. Toxicities (WHO III + IV) were generally tolerable except one toxic death in the control arm and were observed in 9.9% of the patients receiving 5-FU + LEV alone and in 13.3% and in 30.7% of patients receiving additional FA and IFN-α, respectively.

Conclusions:

Addition of IFN-α was associated with increased toxicity without markedly influencing the outcome and should therefore not be recommended for adjuvant treatment. Addition of FA increased the 5-year recurrence-free and overall survival rate by 9.3 and 11.5 percentage points, respectively. 5-FU + LEV + FA for 12 months may be an effective adjuvant treatment option for locally advanced high-risk colon cancer.

 

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bestraling, radiotherapie, darmkanker, foliumzuur


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